PROJECT SUMMARY The Chemical Biology Core (CBC) offers Moffitt Cancer Center (MCC) members access to state-of-the-art technology, instruments, expertise and infrastructure necessary for studying proteins involved in tumorigenesis. The CBC also provides synthetic and medicinal chemistry services for synthesizing chemical probes and to develop lead candidates into compounds that are suitable for pre-clinical cancer efficacy and safety studies. The specific aims of the CBC are to: 1) assist in study design, implementation of synthesis of chemical probes, X-ray crystallography, and protein production via consultation and collaborations; 2) provide members with resources to study the structure of proteins involved in tumorigenesis; and 3) provide access and training on state-of-the-art instrumentation to members. The CBC is composed of two highly specialized sections, Chemistry and Protein Crystallography, which provide services in Synthetic/Medicinal Chemistry, Protein Crystallography, and Biochemistry. The CBC employs five experienced full-time staff, who provide expertise in chemistry, drug discovery and development, protein production, crystallography and biochemistry, and cancer biology. Chemistry services offered by the CBC include: 1) synthesis of focused libraries for hit-to-lead-optimization of new anti-cancer compounds; 2) synthesis of complex small molecules as chemical probes; 3) medicinal chemistry and scale-up synthesis, to provide pre-clinical compounds for potency, selectivity, efficacy and safety studies; 4) analytical chemistry services, to determine physicochemical properties of potent compounds; 5) and synthesis of tagged chemical probes for affinity-based chemical proteomics studies. The CBC also provides support for cloning, expression, large-scale purification of target proteins, X-ray crystallography, high-resolution structure determination, structure-guided synthesis, protein-protein and protein-ligand/drug interactions, and structure of protein-inhibitor complexes. Facilitating this work, the CBC provides members access to high-end instrumentation and associated training. Over the past five years, chemistry, protein production, and crystallography services have supported the projects of 49 members, including services critical for 14 new research grant awards to members. The CBC contributed to 52 publications via synthesis of compounds, protein production, and high-end instrumentation, and core staff were co-authors on the publications of 24 members. During the most recent fiscal year, the CBC provided service for 23 members in four research programs: CBMM (12 members), CBE (6), IMM (3), and CE (2). Regarding use of the CBC, 81% was by peer-review-funded members. The CBC also provided preliminary data, technical sections, and consultation for 21 research proposals during the most recent year. The CBC is supported by institutional and CCSG funds and will continue to provide outstanding chemical biology and state-of-the-art technologies to MCC members.